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Trial registered on ANZCTR


Registration number
ACTRN12607000283471
Ethics application status
Approved
Date submitted
17/05/2007
Date registered
28/05/2007
Date last updated
4/08/2023
Date data sharing statement initially provided
18/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I/II trial to determine safety & efficacy of combination therapy with 5-azacitidine (Vidaza) and Thalidomide in patients with Myelodysplastic Syndromes (MDS)
Scientific title
5-azacitidine and Thalidomide for patients with Myelodysplastic Syndromes to assess safety and efficacy
Secondary ID [1] 370 0
Australasian Leukaemia and Lymphoma Group (ALLG): ALLG MDS3
Universal Trial Number (UTN)
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 1824 0
Condition category
Condition code
Blood 1916 1916 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive both 5-azacitidine and thalidomide:
1. 5-azacitidine subcutaneous injection 75mg/m2/d for 7 days every 28 days for up to 24 cycles
2. Thalidomide orally commencing at 50mg/day, increasing to a maximum 100mg/day continuous treatment for up to 12 months
Intervention code [1] 1765 0
Treatment: Drugs
Comparator / control treatment
-
Control group
Uncontrolled

Outcomes
Primary outcome [1] 2727 0
Haematologic and Non-haematologic toxicity of the combination of thalidomide and 5-azacitidine.
Timepoint [1] 2727 0
Toxicities are measured as they occur throughout the study period.
Secondary outcome [1] 4601 0
Complete response, partial response, haematologic improvement, time to relapse, disease progression, leukaemic transformation or death, change in Quality Of Life parameters, measures of methylation status of various genes, apoptosis and immune modulation.
Timepoint [1] 4601 0
Complete response, partial response, haematologic improvement, Cytogenic response and time to relapse are all measured at Visit 1 of Cycles 3-24, using the modified International Working Group (IWG) criteria.
Secondary outcome [2] 4602 0
Leukaemic transformation or death
Timepoint [2] 4602 0
Is recorded as it occurs throughout the study period.
Secondary outcome [3] 4603 0
Change in Quality Of Life parameters using the European Organisation for Research and Treatment of Cancer (EORTC QLC-C30) and Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaires.
Timepoint [3] 4603 0
Is measured at Screening, Cycle 5 Visit 1 and Cycle 13 Visit 1. Measures of methylation status of various genes, apoptosis and immune modulation, are all measured at Screening, Cycle 2 Visit 4, Cycle 4 Visit 4, Cycle 8 Visit 3, Cycle 12 Visit 3, Cycle 16 Visit 3, Cycle 20 Visit 3, and Cycle 24 Visit 3.

Eligibility
Key inclusion criteria
1. Subjects with myelodysplastic syndrome (MDS), either de novo or treatment related 2. patients with refractory anaemia or refractory anaemia with ringed sideroblasts to meet one of the following additional criteria of marrow dysfunction:a. transfusion dependent or symptomatic anemia up to 3 monthsb. clinically significant thrombocytopenia; either significant bleeding, platelet transfusion dependency or thrombocytopenia with at least two counts less than or equal to 50x109/L at least 1 month apartc. significant neutropenia with absolute neutrophil count = 1.0 x 109/L on at least 2 occasions 1 month apart (those patients with refractory anaemia with excess blasts, refractory anaemia with excess blasts in transformation and chronic myelomonocytic leukaemia are not required to meet the above additional criteria). 4. life expectancy 3 months or over5. Eastern Cooperative Oncology Group performance status 0-26. adequate hepatic function as defined by bilirubin = 1.5 x the upper limit of normal and aspartate aminotransferase & alanine aminotransferase = 2 x upper limits of normal 7. adequate renal function 8. provision of written informed consent prior to registration9. males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and for 30 days following the date of last dose 10. women of childbearing potential may participate providing they agree to use at least 2 effective contraceptive methods throughout the study and for 30 days following completion, and have a negative serum pregnancy test within 21 days prior to commencement of study treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. bone marrow blast count 30% or more2. Grade 3-4 peripheral neuropathy3. prior stem cell transplantation4. prior treatment with thalidomide or its analogues within 30 days of commencing treatment on trial5. any prior treatment with 5-azacitidine, decitabine or any known demethylating agent6. treatment with Granulocyte colony stimulating factor in the 21 days prior to Day 1, androgenic hormones in 14 days prior to Day 1 or any investigational agent in the 30 days prior to Day 17. any serious medical condition which the investigator feels may interfere with the procedures or evaluations of the study8. history of other malignancy within 5 years, except if local disease completely excised with a high probability of cure 9. hepatic tumour or advanced liver disease10. significant cardiac or respiratory disease 11. known active viral infection with human immunodeficiency virus or viral hepatitis B12. known or suspected hypersensitivity to 5-azacitidine, mannitol or thalidomide13. pregnant or breastfeeding females 14. patients unwilling or unable to comply with study protocol15. current participation in another therapeutic clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/06/2007
Actual
1/07/2008
Date of last participant enrolment
Anticipated
Actual
3/07/2009
Date of last data collection
Anticipated
Actual
5/09/2012
Sample size
Target
80
Accrual to date
Final
80
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 2060 0
Commercial sector/Industry
Name [1] 2060 0
Pharmion Australia
Country [1] 2060 0
Australia
Funding source category [2] 2061 0
Charities/Societies/Foundations
Name [2] 2061 0
Leukaemia Foundation
Country [2] 2061 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
-
Country
Australia
Secondary sponsor category [1] 1867 0
None
Name [1] 1867 0
nil
Address [1] 1867 0
Country [1] 1867 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3831 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 3831 0
Ethics committee country [1] 3831 0
Australia
Date submitted for ethics approval [1] 3831 0
Approval date [1] 3831 0
14/05/2007
Ethics approval number [1] 3831 0
07/07

Summary
Brief summary
5-azacitidine, a demethylating agent, has been approved for use in USA for treatment of Myelodysplastic Syndromes (MDS), with overall response rates of approximately 48%, a delay to progression to acute leukaemia or death and an improvement in quality of life. Thalidomide has also shown some activity as a single agent in MDS though with poor tolerance at doses above 100mg/day. Neither of these agents is currently routinely available in Australia for MDS.
This trial aims to show the safety and tolerability of the combination of these two agents in MDS, with responses at least as good as single agent 5-azacitidine, and to investigate further the mechanisms by which these drugs work and whether we can predict which patients may be more likely to respond.
Trial website
Trial related presentations / publications
Melita Kenealy, Nigel Patton, Robin Filshie, Andrew Nicol, Shir-Jing Ho,
Mark Hertzberg, Tony Mills, Ian Prosser, Emma Link, Linda Cowan, Diana Zannino & John F.
Seymour (2016): Results of a phase II study of thalidomide and azacitidine in patients with
clinically advanced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia
(CMML) and low blast count acute myeloid leukemia (AML), Leukemia & Lymphoma, DOI:
10.1080/10428194.2016.1190971
Public notes

Contacts
Principal investigator
Name 27868 0
Address 27868 0
Country 27868 0
Phone 27868 0
Fax 27868 0
Email 27868 0
Contact person for public queries
Name 10954 0
Dr Melita Kenealy
Address 10954 0
c/o Department of Haematology and Medical Oncology
Peter MacCallum Cancer Centre
Locked Bag 1
A’Beckett Street
Melbourne VIC 8006
Country 10954 0
Australia
Phone 10954 0
+61 3 96561111
Fax 10954 0
+61 3 96561408
Email 10954 0
[email protected]
Contact person for scientific queries
Name 1882 0
Dr Melita Kenealy
Address 1882 0
cc/o Department of Haematology and Medical Oncology
Peter MacCallum Cancer Centre
Locked Bag 1
A’Beckett Street
Melbourne VIC 8006
Country 1882 0
Australia
Phone 1882 0
+61 3 96561111
Fax 1882 0
+61 3 96561408
Email 1882 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified IPD data, for all data collected during the trial
When will data be available (start and end dates)?
Data available 3 months following publication, for an indefinite period
Available to whom?
Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.
Available for what types of analyses?
Any type of analysis
Assessed on a case-by-case basis
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19919Study protocol  [email protected] Access can be requested via the Health Data Austra... [More Details]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseHemoglobin is a key determinant of quality of life before and during azacitidine-based therapy for myelodysplasia and low blast count acute myeloid leukemia.2022https://dx.doi.org/10.1080/10428194.2021.2012664
N.B. These documents automatically identified may not have been verified by the study sponsor.